title: RSK isoforms in cancer cell invasion and metastasis.
abstract: Metastasis, the spreading of cancer cells from a primary tumor to secondary sites throughout the body, is the primary cause of death for patients with cancer. New therapies that prevent invasion and metastasis in combination with current treatments could therefore significantly reduce cancer recurrence and morbidity. Metastasis is driven by altered signaling pathways that induce changes in cell-cell adhesion, the cytoskeleton, integrin function, protease expression, epithelial-to-mesenchymal transition and cell survival. The ribosomal S6 kinase (RSK) family of kinases is a group of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) effectors that can regulate these steps of metastasis by phosphorylating both nuclear and cytoplasmic targets. However, our understanding of RSK function in metastasis remains incomplete and is complicated by the fact that the four RSK isoforms perform nonredundant, sometimes opposing functions. Although some isoforms promote cell motility and invasion by altering transcription and integrin activity, others impair cell motility and invasion through effects on the actin cytoskeleton. The mechanism of RSK action depends both on the isoform and the cancer type. However, despite the variance in RSK-mediated outcomes, chemical inhibition of this group of kinases has proven effective in blocking invasion and metastasis of several solid tumors in preclinical models. RSKs are therefore a promising drug target for antimetastatic cancer treatments that could supplement and improve current therapeutic approaches. This review highlights contradiction and agreement in the current data on the function of RSK isoforms in metastasis and suggests ways forward in developing RSK inhibitors as new antimetastasis drugs.
authors.affiliation: Authors' Affiliation: Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
authors.forename: Florian J
authors.initials: FJ
authors.lastname: Sulzmaier
authors.forename: Joe W
authors.initials: JW
authors.lastname: Ramos
mesh_terms: D000818:Animals; D006801:Humans; D007527:Isoenzymes; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D010766:Phosphorylation; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007527:Isoenzymes; D038744:Ribosomal Protein S6 Kinases, 90-kDa